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A Study to Determine the Safety and Efficacy of TG-C in Subjects With Kellgren and Lawrence Grade 2 or 3 OA of the Knee

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ClinicalTrials.gov Identifier: NCT03203330
Recruitment Status : Recruiting
First Posted : June 29, 2017
Last Update Posted : December 3, 2018
Sponsor:
Information provided by (Responsible Party):
Kolon TissueGene, Inc.

Brief Summary:
A randomized, double-blind, placebo-controlled, multi-center, phase 3 study to determine the safety and efficacy of TG-C in subjects with Kellgren and Lawrence Grade 2 or 3 Osteoarthritis of the Knee, Osteoarthritis Research Society International (OARSI) medial joint space narrowing (JSN) Grade 1 or 2 of the knee joint. TG-C is to be administered by a single intra-articular injection to the damaged joint area via ultrasound guidance. Patients will be followed for 24 months for safety and efficacy.

Condition or disease Intervention/treatment Phase
Degenerative Osteoarthritis Biological: TG-C Biological: Placebo Control Phase 3

Detailed Description:
This protocol is designed to assess the safety and efficacy of TG-C in treating symptoms of osteoarthritis of the knee and determining disease modifying effects of TG-C. This study is intended for the treatment of patients with KL Grade 2 and 3 osteoarthritis and OARSI JSN Grade 1 and 2. Assessments will be made on both the symptomatic effects of pain (VAS), function (WOMAC), and Quality of Life (SF-12) as well as the physical effects (JSW, MRI evaluations of whole knee joint organ tissues and structure) and biochemical biomarkers. This is a placebo-controlled study, TG-C will be compared to normal saline as a control. Additionally, this protocol is designed to evaluate the safety of TG-C. Safety will be evaluated by observation of the injection site for irritation or other effects, the incidence and severity of adverse events, and changes in physical examination findings, radiographic criteria, and laboratory tests. Patients will be followed for 24 months for both safety and efficacy.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 510 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Double-blind
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo-Controlled, Multi-Center, Phase 3 Study to Determine the Efficacy of TG-C in Subjects With Kellgren and Lawrence Grade (KLG) 2 or 3 Osteoarthritis of the Knee
Actual Study Start Date : October 30, 2018
Estimated Primary Completion Date : April 30, 2021
Estimated Study Completion Date : April 30, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Osteoarthritis

Arm Intervention/treatment
Active Comparator: Active Treatment (TG-C)
TG-C at 3 x 10e7 cells per single 2 mL intraarticular injection
Biological: TG-C
2 mL injection of allogeneic human chondrocytes expressing transforming growth factor-beta1
Other Name: TissueGene-C

Placebo Comparator: Placebo Control (Normal Saline)
Normal saline, single 2 mL intraarticular injection
Biological: Placebo Control
2 mL normal saline injection
Other Name: Normal Saline




Primary Outcome Measures :
  1. Change in Knee Function as Assessed by the Western Ontario and McMaster Universities Index (WOMAC) [ Time Frame: 12 months ]
    Assessment of change from baseline in target knee function using the WOMAC Osteoarthritis Index. The WOMAC is a proprietary set of standardized questionnaires used by health professionals to evaluate the condition of patients with osteoarthritis of the knee including pain, stiffness, and physical functioning of the joints. The response to the questions is in the form of a checked box associated with the response; None, Mild, Moderate, Severe and Extreme.

  2. Change in Knee Pain as Assessed by VAS [ Time Frame: 12 months ]
    Assessment of change from baseline in target knee pain using the Visual Analog Scale (VAS). The VAS is a method for the assessment of the intensity of pain. The VAS is a horizontal line, 100 mm in length and anchored by word descriptors at each end (no pain, very severe pain). The patient marks on the line at the point that represents their current state. The VAS score is determined by measuring in millimeters from the left hand end to the point of the mark. The score ranges from "0" or no pain to "100" very severe pain.


Secondary Outcome Measures :
  1. MRI Assessment of Target Knee [ Time Frame: 12 months ]
    Evaluation of the features of OA, as determined by structural changes of the knee joint, assessed by MRI

  2. PCS of the SF-12 Questionnaire [ Time Frame: 12 months ]
    Evaluation the Health-Related Quality of Life (HRQoL) as measured by the physical component score (PCS) of the 12-Item Short-Form Health Survey version 2 (SF-12v2®) questionnaire

  3. WOMAC Total Score [ Time Frame: 24 months ]
    Evaluation of the efficacy of TG-C with regard to knee function via WOMAC total score

  4. Health Assessment Questionnaire Disability Index [ Time Frame: 12 months ]
    Evaluation of the HRQoL as measured by the Health Assessment Questionnaire - Disability Index (HAQ-DI)


Other Outcome Measures:
  1. Radiography for Structural Change in Knee Joint [ Time Frame: Through 24 months ]
    Evaluate structural changes of the knee joint as determined by radiography (X-ray)

  2. Efficacy of TG-C with Regard to Knee Function via WOMAC Total Score [ Time Frame: At Months 3, 6, 9 and 18 ]
    Evaluation of the efficacy of TG-C with regard to knee function via WOMAC total score

  3. Efficacy of TG-C with Regard to Knee Function via WOMAC Pain, Function, and Stiffness Scores [ Time Frame: Through 24 months ]
    Evaluate the efficacy of TG-C with regard to knee function via WOMAC® pain, function, and stiffness scores

  4. Efficacy of TG-C with Regard to Knee Function via VAS Pain Score [ Time Frame: At Day 1, Week 1, and Months 1, 3, 6, 9, 18 and 24 ]
    Evaluation of the efficacy of TG-C with regard to knee function via VAS pain score at time points other than Month 12

  5. OMERACT-OARSI Responder Analysis [ Time Frame: 12 and 24 months ]
    Analysis of response using the Outcomes Measures in Rheumatoid Arthritis Clinical Trials (OMERACT)-OARSI responder criteria

  6. International Knee Documentation Committee (IKDC) Scoring of Knee Symptoms, Pain and Function [ Time Frame: 12 and 24 months ]
    Evaluation of target knee symptoms, joint pain, and functionality assessed using the IKDC Subjective knee evaluation

  7. MCS of the SF-12 Questionnaire [ Time Frame: Through 24 months ]
    Evaluation of the change from baseline in the eight domains of the mental component score (MCS) of the SF-12v2 questionnaire

  8. Frequency of Analgesia Use [ Time Frame: Through 24 months ]
    Evaluation of the frequency and dose of analgesia or anti-inflammatory medication use

  9. Structural Changes to the Knee Joint as determined by WORMS and MOAKS [ Time Frame: Through 24 months ]
    Evaluation of the structural changes of the knee joint as determined by Whole-Organ Magnetic Resonance Imaging Score (WORMS) semi-quantitative scoring system and partial MRI Osteoarthritis Knee Score (MOAKS)

  10. Biochemical Biomarker Analysis [ Time Frame: Through 24 months ]
    Assessment of changes from baseline in biochemical biomarkers of knee osteoarthritis

  11. Incidence and Severity of Adverse Events (AEs) [ Time Frame: Through 24 months ]
    Incidence and severity of adverse events assess after treatment

  12. Changes in Laboratory Tests [ Time Frame: Through 24 months ]
    Changes from baseline in clinical laboratory test results

  13. Radiography for Osteophytes [ Time Frame: 12 and 24 months ]
    Radiography for assessment of change from baseline in osteophytes by OARSI criteria

  14. Knee-related RHCU and Costs [ Time Frame: Through 24 months ]
    Evaluation of the knee-related health care utilization (RHCU) and costs



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Ages Eligible for Study:   40 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Aged 40 or older
  • BMI between 18.5 and 40
  • KL Grade 2 or 3 knee OA
  • OARSI Grade 1 or 2 medial JSN
  • Pain >= 40 on VAS scale
  • WOMAC score <=70 for target knee
  • Written informed consent
  • Using birth control

Exclusion Criteria:

  • Knee symptoms that result in difficulty or inability to walk
  • Knee effusion >2+
  • Has Grade 0 OARSI JSN or atrophic OA
  • Has a score of >=5 on the cartilege feature of the WORMS at Screening
  • MRI exam indicates fracture or tumor
  • Has a positive result on RCR testing at Screening
  • Has taken NSAIDS with 14 days of baseline
  • Has taken steroidal anti-inflammatory medication within 2 months of baseline
  • Currently using topical analgesics on target knee
  • Chronic (>21 days) narcotic use
  • Recent history (within 1 year) of drug or alcohol abuse
  • Pregnant or lactating
  • Has received injection to target knee within 2 months prior to study entry
  • Is contraindicated or cannot undergo for 3 Tesla (3T) MRI
  • History of various disorders of the knee including but not limited to rheumatoid arthritis, psoriatic arthritis, autoimmune OA, chondrocalcinosis, gout, hemochromatosis, villonodular synovitis, or synovial chondromatosis
  • Severe hip osteoarthritis ipsilateral to the target knee
  • Ongoing infection disease including but not limited to HIV, Hepatitis B or C.
  • Clinically significant congestive heart failure hepatic disease, kidney disease, adrenal insufficiency, acromegaly, uncontrolled hyper- or hypothyroidism, or non-specified uncontrolled endocrine disorder
  • Uncontrolled diabetes based on a HbA1c > 8% at screening
  • At risk for post procedure bleeding or infection
  • Is taking anti-platelets or anti-coagulants (low-dose aspirin permitted)
  • Has had an active malignancy with the last 5 years
  • Previous cartilage repair procedures
  • Major injury to the target knee within 12 months of screening
  • Active ulcer or infection on the skin of the target knee within 1 month of screening
  • Surgery on the target knee within 6 months of screening
  • Valgus or varus of the target knee >10 degrees
  • Has total knee arthroplasty or other knee surgery planned within the next 12 months.
  • Participation in another investigation study within 3 months
  • Unable to complete requisite follow-up and 3T MRI exams
  • Has cognitive impairment or cannot otherwise provide informed consent or answer questionnaires.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03203330


Contacts
Contact: Robert Casper, MS (301) 921-6000 ext 173 rcasper@tissuegene.com
Contact: Raymond Touomou (301) 921-6000 ext 196 RTouomou@tissuegene.com

Locations
United States, Pennsylvania
Altoona Center for Clinical Research Recruiting
Duncansville, Pennsylvania, United States, 16635
Contact: Alan Kivitz, MD         
Sponsors and Collaborators
Kolon TissueGene, Inc.
Investigators
Study Chair: Bumsup Lee, DVM, PhD Kolon TissueGene, Inc.

Responsible Party: Kolon TissueGene, Inc.
ClinicalTrials.gov Identifier: NCT03203330     History of Changes
Other Study ID Numbers: TGC12301
First Posted: June 29, 2017    Key Record Dates
Last Update Posted: December 3, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Osteoarthritis
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases